title: Hypoxia inducible factor-1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study.
abstract: BACKGROUND
  Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1α (HIF-1α) was correlated with hepatic metastases in PDAC.
  
  
  METHODS
  We examined the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A), thymidine phosphorylase (TP) and basic fibroblast growth factor (bFGF) in a total of 100 paraffin-embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count (MVC) and apoptotic index (AI), and assessed their correlations with hepatic metastases. Student's t-test, the Mann-Whitney U-test, and Spearman correlation coefficients were used to validate the model, and regression analysis was used to test the model.
  
  
  RESULTS
  Hypoxia inducible factor-1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI. HIF-1α expression (P = 0.0087) and angiogenic factors (P = 0.0079) were significantly associated with not only the microvessel status (P = 0.022) but also the high incidence of hepatic metastasis (P = 0.02), resulting in the worse survival of PDAC patients (P < 0.05).
  
  
  CONCLUSIONS
  Hypoxia inducible factor-1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.
authors.affiliation: Department of Digestive, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Desaki
authors.forename: Kosei
authors.initials: K
authors.lastname: Maemura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mataki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shinchi
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.forename: Sonshin
authors.initials: S
authors.lastname: Takao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011743:Pyrimidines; D013449:Sulfonamides; D013939:Thymidine Phosphorylase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011743:Pyrimidines; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C588062:oclacitinib; D013939:Thymidine Phosphorylase
keywords: Hypoxia inducible factor-1α; Microvessel count; Pancreatic cancer; Thymidine phosphorylase; Vascular endothelial growth factor